Advocating hormonal treatment to prevent adult in-fertility in patients diagnosed with congenital un-descended testes.

In 2007 the Nordic group came to the following unanimous conclusions: In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long-term adverse effects on spermatogenesis. Thus, surgery is to be preferred. However, defective mini puberty inducing insufficient gonadotropin secretion is one of the most common causes of nonobstructive azoospermia in men suffering from congenital isolated unilateral or bilateral cryptorchidism. The extent of alteration in the unilateral undescended testis correlate with the contralateral descended testis, indicating that unilateral cryptorchidism is a bilateral disease. Idiopathic central hypogonadism explains the phenomenon of defective mini puberty in otherwise healthy cryptorchid boys. We therefore recommend hormonal treatment for cryptorchid boys with defective mini puberty. Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. At the molecular level, there is no convincing evidence that heat shock is responsible for the observed pathological testicular changes. Thus, impaired transformation of gonocytes is not the result of temperature stress but rather a hormonal imbalance. Cryptorchidism should therefore be considered a serious andrological problem that cannot be successfully treated by early orchidopexy alone.

Low-dose every-second-day LHRH treatment following bilateral orchidopexy in children with bilateral cryptorchidism may improve their fertility outcome.

INTRODUCTION/BACKGROUND: Currently the standard treatment for bilateral cryptorchidism is bilateral surgical orchidopexy. Whether a hormonal treatment should be routinely administered postoperatively to increase fertility is debatable. Low-dose postoperative luteinizing hormone releasing hormone (LHRH) can increase spermatogonial numbers, but the effect of native LHRH (Kryptocur®) on adult fertility is unclear. OBJECTIVE: To determine if low-dose every-second-day postoperative LHRH administration in children with bilateral cryptorchidism improves fertility in adulthood and if Nistal testicular histological grading could guide the decision to administer LHRH. STUDY DESIGN METHODS: All patients, actually at least 16yr of age, that underwent a bilateral orchidolysis and orchidopexy for bilateral cryptorchidism (surgery between 1997 and 2018) were contacted and offered a clinical exam, hormone levels, sperm analysis, and a scrotal ultrasound. At the original surgery, testicular biopsy was performed (if 60% of the tubuli contain >1 spermatogonia, this is normal = Nistal-1, if 30-60% filled = Nistal-2, if <30% = Nistal-3 and if Sertoli only = Nistal-4) and if in at least one testis impaired. A low dose native LHRH treatment was offered to the patients, as this treatment is known to increase the number of spermatogonia in a short term. Kryptocur® (LHRH, Gonadorelin, Hoechst®) was prescribed and dosed at 200 µg (one spray in one nostril) every other day for 6-8 months. RESULTS AND LIMITATIONS: Forty-two men were eligible for this study. 20/42 accepted the invitation for a clinical and hormonal evaluation. 16/20 men accepted the invitation for an additional sperm analysis. Fourteen of 20 men received low-dose LHRH postoperatively in a nonrandomized manner. Three men had Nistal grade 1, eight grade 2, seven grade 3, and two had grade 4. Inhibin B levels were higher in men with Nistal 1 and 2 compared with Nistal 3 and 4 P ≤ 0.037). Severe oligospermia/azoospermia (<1 × 106/ejaculate) was observed in 33% of the treated group vs 67% of the untreated group (P ≤ 0.036.) DISCUSSION AND CONCLUSIONS: Low-dose every-second-day postoperative LHRH treatment improves fertility outcome in bilateral cryptorchidism. Histological analysis of prepubertal testes according to Nistal grading cannot be used as a predictive diagnostic test for LHRH treatment.

The effect of curcumin on NRF2/Keap1 signalling pathway in the epididymis of mouse experimental cryptorchidism.

Nrf2/Keap1 pathway, which prevents cellular damage against reactive oxygen species production, is disrupted in epididymis following cryptorchidism. In this study, we aimed to use curcumin (Cur) as an activator of Nrf2 to decrease the effects of disruption in this pathway caused by cryptorchidism. In this study, animals were randomly divided into following groups: control, sham-surgery, sham-vehicle, sham-Cur50, sham-Cur100 , cryptorchidism, cryptorchidism-vehicle, cryptorchidism-Cur50 and cryptorchidism-Cur100 . For cryptorchidism induction, the left testicle was removed from the scrotum and sutured to the abdominal wall. Two weeks after surgery, Cur was given orally to animals. After 1 month, sperm parameters and testis histopathology were analysed. The expression of Nrf2, NQO1, HO1, and Keap1 genes was evaluated by real-time polymerase chain reaction. Our data showed that Cur, especially at high doses, could improve sperm parameters and testis histopathology, which were damaged following cryptorchidism induction. The expression of HO1, NQO1, and Nrf2 genes, which had decreased in the cryptorchidism group, showed a significant increase after administration of Cur in a dose-dependent manner. Cur, by inducing the expression of genes involved in the Nrf2/Keap1 pathway, could reduce the adverse effects of cryptorchidism and might be used as adjuvant therapy for decreasing cryptorchidism complications before surgery.

16 years follow-up evaluation of immediate vs delayed vs. combined hormonal therapy on fertility of patients with cryptorchidism: results of a longitudinal cohort study.

BACKGROUND: To investigate in a longitudinal cohort study, the best treatment to preserve fertility in cryptorchid subjects. Patients treated with immediate hormonal vs. delayed vs. combined (hormone plus surgery) therapy consecutively enrolled during the period 1987-1997, were evaluated. METHODS: Two hundred fifty-five subjects were enrolled and 192 patients completed the follow-upt. One hundred fifty-six patients and 36 out 192 had monolateral and bilateral cryptorchidism, respectively. Twenty-nine out of 192 were previously treated by surgery alone (Group A), 93/192 by hormone therapy alone (Group B), 51/192 received sequential combined hormone therapy plus surgery (Group C) whilst 19/192 refused any type of treatment (Group D). The other 63 patients were considered lost to follow-up. All the patients underwent medical consultation, scrotal ultrasound scan, sperm analysis and Inhibin B, Follicular Stimulating Hormone (FSH) and Testosterone (T) serum level determination. RESULTS: Testicular volume was found decreased in the Group D patients whilst hormone serum levels were comparable in all groups. Statistically significant differences for sperm characteristics were found in patients treated with hormonal therapy alone or combined with surgery (Groups B and C). These two groups reported better semen quality than patients who received surgery alone or no treatment. No differences were observed between monolateral and bilateral cryptorchidism patients. CONCLUSIONS: Early prolonged hormonal therapy is advisable in all patients with cryptorchidism independently from the surgical option of promoting testicular descent to the scrotum. Hormonal therapy provides in our study better chance to obtain adequate sperm quality in adult life.

The protective effect of curcumin on testicular tissue in a cryptorchid rat model.

BACKGROUND: Cryptorchidism is the most common abnormality of male sexual development. For the protection of testicular functions, antioxidants have emerged as novel options. This study aimed to investigate the protective effect of curcumin (Cur), a strong antioxidant, on the Flutamide-induced cryptorchidism testicular tissue. MATERIALS AND METHODS: Pregnant rats were randomly allocated to 3 groups (n = 10, each): a control, a model, and a Cur-treated group (100 mg/kg/d). All offspring were delivered by days 21-22 of gestation and the male rats were sacrificed at postnatal birth days (PNDs) PND60. The testicles were separated and weighed, followed by TUNEL staining to detect germ cell apoptosis, an ELISA kit to measure SOD and MDA, and Western blot analysis to evaluate the expression of Bax, Bcl-2, and PCNA. RESULTS: Curcumin administration ameliorated the histological appearance of the testis and greatly reduced the level of apoptosis in cryptorchidism rats' testicular cells. After curcumin treatment, the expression of proliferating cell nuclear antigen (PCNA) was restored in the testis tissues of cryptorchidism rats. Curcumin therapy reduced Bax expression while increasing Bcl-2 expression, according to the molecular study. Curcumin therapy also reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) levels in cryptorchidism rats' testis tissue. CONCLUSIONS: It can be concluded that curcumin administration significantly reduced the germ cell apoptosis in rats with cryptorchidism, which provides new insight for antioxidant therapy in preserving testicular functions before or after surgery in cryptorchidism.

The safety of neoadjuvant hormonal treatment in infants with cryptorchidism.

BACKGROUND/PURPOSE: The standard treatment for boys with non-syndromic cryptorchidism is an early orchidopexy. It is unclear if surgical intervention alone is enough for future fertility. Recent studies show benefit of neoadjuvant or adjuvant hormonal treatment with gonadorelin (GnRH) for spermatogonia maturation based on testicular biopsy. The aim of this prospective study was to assess the safety of this treatment in infants with undescended testis at the recommended timing of early gonadorelin administration and timing of orchidopexy. METHODS: Unilateral cryptorchid full term boys were initially examined (including hormonal, physical and ultrasound examination) at the age of 2.5-3.5 months. At 6 months of age, cryptorchidism was confirmed. Those with non-syndromic cryptorchidism and palpable or sonographically detected testis were randomly assigned into two groups: with and without intranasal gonadorelin treatment. Inclusion criteria were met by 36 boys (21 in GNRH and 15 in the control groups). The following orchidopexy was performed before 12 months of age with repeated examination at time of surgery. Penile size and testicular volume (using ultrasound) and basal serum levels of LH, FSH, testosterone, Inhibin B and AMH were recorded at age of 3.0 (mean) months and 11.0 (mean) months (date of surgery). The stimulation hormonal levels were checked during GnRH administration. RESULTS: Between minipuberty (mean 3 months) and time of orchidopexy (mean 11 months of age) the penile size increased significantly and similarly in both groups. There was no significant difference in the change of the volume of descended testis between the groups nor of the volume of undescended testis. In addition, we did not find any significant difference in the change (drop) of hormonal levels of LH, FSH, Testosterone, Inhibin B and AMH (Table 1a) CONCLUSION: The neoadjuvant gonadorelin stimulation in infants with unilateral undescended testis has not shown any specific effect on the development of penile size, testicular volume and hormonal levels at time of orchidopexy in comparison with boys without stimulation, and in the mid-term, this treatment can be considered safe. Further follow-up is necessary to evaluate the long-term effect of this early treatment.

Current concepts surrounding neonatal hormone therapy for boys with congenital hypogonadotropic hypogonadism.

INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) is a genetic disorder of reproduction and development, characterized by deficient gonadotropin-releasing hormone (GnRH) secretion or action, affecting 1-in-4,000-15,000 males. Micropenis and undescended testes are cardinal features of antenatal GnRH deficiency and could indicate absent minipuberty in the first postnatal months. In this review, we outline the pathophysiology and clinical consequences of absent minipuberty and its implications for optimal approaches to the endocrine management of affected boys. AREAS COVERED: Deficient GnRH activity during fetal development and neonatal-infancy phase of minipuberty accounts for the diminished mass of Sertoli cells and seminiferous tubules among CHH males, enduring impairment of reproductive function even during gonadotropin replacement in adult life. In overcoming this obstacle, several clinical studies of neonatal gonadotropin replacement have consistently shown positive results in inducing testicular development and correcting cryptorchidism. EXPERT OPINION: A high index of clinical suspicion, combined with hormonal testing undertaken in the postnatal period of 1-4 months, can reliably confirm or refute the diagnosis of CHH. Timely identification of CHH in affected male infants (having characteristic "red flag' developmental anomalies) opens up the possibility for gonadotropin replacement as a targeted therapy to restore the normal hormonal milieu of minipuberty. Further work is necessary in formulating optimal gonadotropin treatment regimens to be more widely adopted in clinical practice.

Hormonal therapy is effective and safe for cryptorchidism caused by idiopathic hypogonadotropic hypogonadism in adult males.

Background: Hormonal therapy is a reasonable treatment for cryptorchidism caused by idiopathic hypogonadotropic hypogonadism (IHH). However, the clinical evidence on whether it is effective and safe for the treatment of cryptorchidism caused by IHH is lacking. Aim: To evaluate the effect of hormonal therapy in testicular descent, puberty development, and spermatogenesis in adult males with cryptorchidism caused by IHH. Methods: This retrospective study included 51 patients with cryptorchidism caused by IHH from the Andrology Clinic of University affiliated teaching hospital. Patients were divided into two groups: group A patients received hormonal therapy; group B patients received surgical treatment for cryptorchidism followed by hormonal therapy. Results: The rate of successful testicular descent following hormonal therapy (19/32 in group A) or surgical treatment (11/19 in group B) shows no statistically significant difference. There was also no statistically significant difference in penile length, Tanner stage of pubic hair, testicular volume, and success rate of spermatogenesis between the two groups. Testicular atrophy was seen in a single patient in group B. Conclusions: Hormone therapy in adult males with cryptorchidism caused by IHH is effective and safe regarding testicular descent, puberty development, and spermatogenesis. This study provides new insight into the treatment of cryptorchidism caused by IHH and highlights that hormonal therapy could be an effective, safe, and economic treatment option for cryptorchidism in males caused by IHH.

Gonadotropins for testicular descent in cryptorchid congenital hypogonadotropic hypogonadism males beyond infancy.

OBJECTIVES: To study the effect of combined gonadotropin therapy (CGT) on testicular descent ± spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) patients with cryptorchidism beyond infancy. METHODS: This retrospective cohort study included CHH patients with cryptorchidism [bilateral (n=5) or unilateral (n=1)] treated with CGT for testicular descent ± pubertal induction. All participants were treated with CGT [human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG)] with hMG pretreatment in three and monitored for changes in testicular volume (TV), serum total testosterone (T), serum inhibin-B, and sperm concentration. RESULTS: Complete testicular descent to the scrotal position was achieved in 5/6 patients (10/11 testes) after 4.7 ± 1.6 months of treatment. There was 44 ± 18%, 97.5% (IQR: 44-195), 10-fold (IQR: 3-19.6), and two-fold (IQR: 1.7-9.3) increase in stretched penile length, ultrasound measured TV, T level, and serum inhibin-B from baseline, respectively. In two pediatric cases, testicular descent occurred with isolated hMG therapy. At the last follow up (median: 23.5, IQR: 10.5-38.7 months), all the descended testes remained in scrotal position. In four pubertal/postpubertal age patients, continuous CGT (18-60 months) yielded T and inhibin-B levels of 16.64 ± 1.46 nmol/l and 106 ± 32.6 pg/mL, respectively. All the three patients with available semen analysis had sperm concentration of ≥5 million/mL and one of them achieved paternity. CONCLUSIONS: A trial of CGT before orchiopexy may be considered in CHH males with cryptorchidism even beyond the narrow age-window of infancy. CGT may also have beneficial effects on future spermatogenesis and fertility outcomes in these patients.

Efficacy of topical testosterone in management of scrotal hypoplasia and agenesis.

BACKGROUND: Scrotal hypoplasia or agenesis may posses difficulty during orchidopexy or end with social anxiety around excessively small scrotal size when compared to peers, and where there may be concerns regarding the future sexual life. OBJECTIVE: Any conservative modality applicable to ameliorate scrotal underdevelopment partially or completely will be useful either solely or before reconstructive surgery. STUDY DESIGN: Seventeen child (3-8 years) were diagnosed with bilateral scrotal hypoplasia (SH) in 5 unilateral in 7, bilateral scrotal agenesis (SA) diagnosed in 4 cases, and unilateral in one. Testicles are either undescended, ectopic, or normal. All cases managed by Testogel 1% topical testosterone for 4 weeks. Clinical assessment by measurements of the scrotal skin surface area (scrotal length multiplied by width) and scrotal corrugations counting. Inguinal and renal ultrasound done for all cases and karyotyping for cases of agenesis and cases with bilateral undescended testicles. Total and free testosterone, LH, FSH and AMH hormones were assisted before treatment, weekly and one week after therapy. Data analyzed and evaluated, difference of means used to test for statistically significant differences between scores of scrotal development. RESULTS: Free and total testosterone elevated in the 1st week of treatment, but restored to normal or higher levels in 60% of cases at the 2nd week. Satisfactory response (Increasing numbers of scrotal rugae or scrotal surface area by 30-50% above the pretreatment status) obtained in 85% and 60% of unilateral and bilateral SH, but only a partial response (10-20% increase) was gained in 40% of cases with agenesis. No major adverse effect was appreciated. DISCUSSION: Response of some cases of SH to topical testosterone indicates presence of remnants of labioscrotal folds with testosterone receptors (Bell et al., 1971) [1]. Testosterone replacement therapy can improve the signs and well-being of a hypogonadal male by restoring serum testosterone concentrations to physiologic levels. In this study the mean average testosterone concentration one week after application of testogel was 13.47 ± 2.45 and 12.12 ± 2.5 within 2nd, 4th week, and after cessation of treatment. Anti-Mullerian hormone is significantly low in 12 cases; mainly in cases of SA (P-value <0.001). CONCLUSION: Short term topical testosterone proved to be effective in a considerable percentage of cases of either bilateral or unilateral scrotal hypoplasia; with a subsequent increase in scrotal surface area and number of rugae, it may substitutes the indication for surgical reconstruction. Long term follow up is a limitation of this study.

Metabolomics analysis reveals metabolic changes associated with trans-resveratrol treatment in experimental cryptorchidism mice.

This study aimed to analyse global metabolomic changes associated with trans-resveratrol (RSV) treatment in mice with cryptorchidism using untargeted metabolomics. Cryptorchidism was established surgically in Kunming mice, which were then treated with 20µg g-1 day-1, s.c., RSV for 35 consecutive days. Typical manifestations of spermatogenesis arrest were seen in mice with cryptorchidism, and RSV treatment for 35 days restored spermatogenesis. Liquid chromatography-tandem mass spectrometry was used to profile the metabolome of testes from mice in the control (non-cryptorchid, untreated), cryptorchid and RSV-treated cryptorchid groups. In all, 1386 and 179 differential metabolites were detected in the positive and negative modes respectively. Seven and six potential biomarkers were screened for spermatogenesis arrest and restoration respectively. Pathway analysis showed changes in 197 metabolic pathways. The hexosamine biosynthesis pathway was inhibited in the cryptorchid group, which probably resulted in a decrease in the end product, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Immunoblot analysis showed that total testicular protein O-linked ß-N-acetylglucosamine glycosylation was related to spermatogenesis arrest, further indicating a decrease in UDP-GlcNAc in the cryptorchid group. Thus, untargeted metabolomics revealed the biochemical pathways associated with the restoration of metabolic status in the cryptorchid group following RSV treatment and the findings could be used to monitor the response to RSV treatment. This study provides a meaningful foundation for the future clinical application of RSV in the treatment of spermatogenesis dysfunction.

A pilot clinical trial with losartan in Myhre syndrome.

INTRODUCTION: Myhre syndrome (MS) is an ultra-rare disorder due to pathogenic variants in the SMAD4 gene that encodes a protein regulating the TGF-ß pathway and extra-cellular matrix (ECM) homeostasis. Main clinical features of MS include thickening of skin and joint stiffness. Previous studies showed that losartan improved ECM deposition in MS fibroblasts. MATERIALS AND METHODS: Four molecularly confirmed MS subjects (mean age 23.8 ± 17 years) were evaluated for: (a) skin thickness by Rodnan score, (b) joint range of motion (ROM) by goniometry, and (c) speckle-tracking echocardiogram. Following baseline evaluations, three MS individuals received losartan for 12 months and pre-defined endpoints were monitored after 6 and 12 months of treatment. RESULTS: At baseline, Rodnan scores were increased, joint ROM was reduced, and speckle-tracking echocardiogram revealed reduced myocardial strain. In three MS subjects, improvements in skin thickness, joint ROM and to a lesser extent of myocardial strain, were observed after 6 and 12 months of losartan treatment. CONCLUSIONS: Although further long-term controlled clinical trials with a larger number of affected individuals are needed, the present study suggests that losartan might improve skin, joint and heart abnormalities of MS.

The ameliorative effect of curcumin on cryptorchid and non-cryptorchid testes in induced unilateral cryptorchidism in albino rat: histological evaluation.

BACKGROUND: Cryptorchidism, one or both hidden testes, is the most common abnormality of male sexual development. Subfertility or infertility is associated with both unilateral and bilateral cryptorchidism. In this study, we investigate the possible ameliorative effect of curcumin (Cur) on the induced-unilateral cryptorchidism testicular injury in both cryptorchid (Cryp) and non-cryptorchid (non-Cryp) scrotal testes through histological, immunohistochemical and morphometrics. MATERIALS AND METHODS: Forty adult male albino rats were divided into: control group, Cur control group, Cryp group, and Cryp+Cur group. The rat model was surgically established by fixing the left testis in the abdomen. The treated groups were subjected to surgically induced-unilateral cryptorchidism on the left side then were given Cur (80 mg/kg) orally, for 20 days. Histological analysis using haematoxylin and eosin and periodic acid Schiff's reaction was done. Immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA); to estimate the proliferation in the germinal epithelium, and vimentin; to evaluate Sertoli cells. The results were confirmed by statistical evaluation of the spermatogenic epithelium height, the seminiferous tubules diameter, the basement membrane thickness, the number of PCNA immunostained cells and the area per cent of vimentin immunostaining. RESULTS: Distorted seminiferous tubules, substantial degeneration of the germinal epithelium, thickening of the basement membrane with a significant decrease in PCNA and vimentin immunostaining were observed in Cryp group; mainly in the cryptorchid testis. These structural changes were significantly reversed in Crypt+Cur group. CONCLUSIONS: Curcumin proved to be an important and effective medical line for protecting against the unfavourable sequels of cryptorchidism in a rat model.

[Hormonal therapy for undescended testes: an outdated concept?] / Ist die Hormontherapie bei Hodenhochstand noch zeitgemäß?

For decades, hormonal therapy was considered an integral part of the treatment regimen for undescended testes, particularly in Europe. However, the available data are controversial. According to many studies and a large meta-analysis, testicular descent can only be achieved in approximately 20 % of cases, whereas a few small studies report better results. Improvement of fertility is also considered significant in some studies, while others even report detrimental effects. Meanwhile, the recommendations for the use of hormonal therapy have been removed from most international guidelines. In Germany, hormonal therapy is only recommended for a limited number of indications. It is widely accepted that hormonal therapy has no particular value in the induction of testicular descent, and even the possible improvement of fertility in cases of bilateral undescended testes is regarded with some caution. In light of the controversial and weak data, it is questionable if hormonal therapy should still be recommended.

[Hormonal treatment of undescended testes]. / Hormontherapie bei Hodenhochstand.

Undescended testes are a very common congenital problem of the urogenital tract. Altered spermatogenesis and fertility as well as an elevated risk for oncologic degeneration are known facts associated with testicular malposition. There is broad international consensus among the various disciplines that the treatment of undescended testes should be completed by the age of 12 months. Following the guideline of the German Working Group of Scientific Medical Societies (AWMF), hormonal treatment should be offered to patients with bilateral undescended testicles. This article reviews the literature and disputes the reasoning of the recommendation to treat undescended testes hormonally.

[AN ADULT MALE CASE OF CRYPTORCHIDISM CONCOMITANT WITH HYPOGONADOTROPIC HYPOGONADISM WHO UNDERWENT hCG THERAPY AND SHOWED A SPONTANEOUS DESCENT OF THE TESTIS].

A 32-year-old Japanese man was referred to our hospital with a chief complaint of the delayed puberty with having been aware of it since he was in his teens. Physical examination demonstrated the small penis, the impalpable left testis, and the atrophic right testis in the scrotum. Abdominal magnetic resonance imaging showed the left testis of 8 mm in the external inguinal ring. Endocrinological blood tests revealed that testosterone and luteinizing hormone were 0.34 ng/mL and 1 mIU/mL, respectively, leading to a diagnosis of the left cryptorchidism with hypogonadotropic hypogonadism. The hCG therapy was initiated, resulting in the increased volume and spontaneous descent into the scrotum of the left testis after 6 months of the treatment. The hCG therapy could be an alternative treatment for surgery for cryptorchidism with hypogonadism in adults.

Antagonistic Effect of Cuscuta chinensis on a Rat Model with Unilateral Cryptorchidism.

BACKGROUND The aim of this study was to investigate the effect of Cuscuta chinensis Lam. on germ cell apoptosis in a rat model of unilateral cryptorchidism. MATERIAL AND METHODS Thirty male SD rats were randomly and equally divided into a control group, a model group, and a Cuscuta group (5.0 g/kg/d) (n=10). The rat model of unilateral cryptorchidism in the model and Cuscuta groups was established by removal of the right gubernaculum, while rats in the control group received no treatment. After modeling, rats in the Cuscuta chinensis group were intragastrically administered Cuscuta chinensis extract (5.0 g/kg/d), while rats in the control group and model group were administered an equal volume of normal saline. After 90 days, all the rats were sacrificed and the testicles were separated and weighed, followed by TUNEL staining to detect germ cell apoptosis, flow cytometry to measure JC-1, ROS, and MDA, and Western blot analysis to evaluate the expression of Bax, Bcl-2, and cleaved caspase3. RESULTS Ninety days after the operation, Cuscuta chinensis Lam significantly minimized the damage caused by modeling by increasing weight of testis, reducing the germ cell apoptosis, and enhancing the mitochondrial membrane potential of testicles, as shown by levels of JC-1, ROS, and MDA, as well as elevating the level of Bcl-2/Bax and reducing the level of cleaved caspase3 (P<0.05). CONCLUSIONS Treatment with Cuscuta chinensis Lam reduced the germ cell apoptosis in rats with unilateral cryptorchidism, which provides new insight for the development of cryptorchidism therapy in the future.

Retinoic acid: A potential therapeutic agent for cryptorchidism infertility based on investigation of flutamide-induced cryptorchid rats in vivo and in vitro.

Cryptorchidism is a common disorder in children and may cause infertility in adults. The BTB is essential for maintaining the microenvironment necessary for normal spermatogenesis. This study investigated whether retinoic acid (RA) may regulate the proteins that are essential for integrity of the BTB in cryptorchidism. Female Sprague-Dawley rats were administrated flutamide during late pregnancy to induce a model of cryptorchidism in male offspring. The concentrations of RA and BTB tight and gap junction protein levels were significantly lower in untreated cryptorchid pups compared with normal pups, but almost normal in cryptorchid pups given RA. Studies in vitro corroborated these findings. The sperm quality of RA-treated model pups was better compared with the untreated model. RA treatment may have therapeutic potential to restore retinoic acid and proteins associated with integrity of the BTB in cryptorchid testis.